Investigations of the pathogenesis and treatment of lupus nephritis are facilitated by the availability of inbred strains of mice that develop disease similar to human systemic lupus erythematosus. The natural evolution of the diverse histologic features of murine lupus nephritis has been studied to delineate the types of glomerular and tubulointerstitial lesions. Innovative treatment strategies will be studied to refine our approach to this disease. The impact of biologic response modifiers on immunologic features will be investigated as well. Clinical, histologic and immunologic outcome parameters will be evaluated including detailed studies of renal morphology, and the characteristics of spleen lymphocytes employing flow cytometry, measures of immunoglobulin gene expression, and in vitro assays of alterations in humoral and cell mediated immune regulation. An investigation of the effects of a monthly doses of intraperitoneal cyclophosphamide in NZB/W female mice has been undertaken. Multiple doses of "pulse" cyclophosphamide lead to prolonged effects on the numbers (total and phenotypes) and the functions (spontaneous immunoglobulin secreting cell responses) of lymphocytes (spleen and peripheral blood). Additional studies regarding the mechanisms underlying these effects are in progress.